Facioscapulohumeral muscular dystrophy (FSHD) is the third most common form of muscular dystrophy. Although the genetic lesion is well described, neither the specific gene(s) nor the cellular mechanism involved in its pathophysiology are known. We propose to investigate the molecular and cellular pathophysiology of facioscapulohumeral muscular dystrophy (FSHD) utilizing the techniques of microarray analysis of skeletal muscle samples with followup biological confirmation of relevant dysregulated genes using real time RT-PCR and immunohistochemical techniques. The research proposal will test the hypotheses that in FSHD (1) critical deletion in D4Z4 heterochromatic repeats results in altered expression of adjacent 4q35 genes, and that (2) aberrant overexpression of vascular genes, either as a primary or downstream effect, is involved in the pathogenesis of this disease. The ultimate goal is to identify critical, causal disruptions in cellular function that are amenable to therapeutic intervention.